Project Summary When seeking blood, mosquito species are often biased toward one host over others, and this can significantly impact their likelihood of transmitting disease to humans. It is becoming increasingly clear that host seeking biases are genomically based, but significant gaps in our knowledge of the exact genomic drivers of these biases still exist. In the case of Culex pipiens, very little is known about what genes drive host location and feeding behaviors, and yet they are the primary vectors of West Nile virus (WNV) to humans across the Northeastern United States. WNV is typically transmitted from bird to bird by the bite of a Cx. pipiens mosquito, but human outbreaks occur annually. The two inter-fertile forms of Cx. pipiens, known as true pipiens and molestus, complicate the WNV transmission picture. True pipiens breeds above ground and is thought to primarily feed on birds, while molestus breeds below ground near human habitations, and feeds on mammals, including humans. The current paradigm is that interbreeding between molestus and the above ground pipiens forms leads to heightened human WNV transmission. Our research aims to empirically test this paradigm by: 1) quantifying the behaviors of above ground pipiens, below ground molestus and their hybrids in response to avian and mammalian hosts, and linking host choices to underlying genomic regions in a laboratory setting, 2) field-collecting avian and mammal-fed Cx. pipiens to determine which regions of the mosquito genome are associated with divergent host feeding, and 3) using a well-established epidemiological model to measure the effect of hybridization between the avian- and mammalian-feeding forms of Cx. pipiens on WNV transmission risk in humans.